Biosimilars law in Germany draws legitimate criticism

The new legislation

The new law for greater safety in the supply of pharmaceuticals was proposed by Germany's Ministry of Health last November in response to a number of scandals to have hit the industry in recent times, including in respect of contaminated medicines.

The legislation addresses not just safety-related aspects but also other important and widely discussed topics like e-prescription. The provisions on pharmacy-level substitution for biological drugs are perhaps the most controversial, however.

Biologics contain active substances derived from biological sources, such as human cells, and are among the most expensive therapies available. Due to the variability of biologicals caused by the manufacturing process, there are stricter rules around substitution of those medicines than those that apply to the substitution of small molecule generic medicinal products.

According to current law in Germany, pharmacists can only substitute a biological if the biological is obtained in a manufacturing process identical to that of the reference pharmaceutical – these are known as so-called bioidenticals.

The new law, however, will give new powers to Germany's Federal Joint Committee (G-BA), a decision-making body made up of physicians, dentists, hospitals and health insurance funds, to specify cases in which biologicals can be substituted in pharmacies with biosimilars.

Biosimilars are medicines that are based on original biologicals and which are launched after patent expiry. They are similar to the originator products but are by no means identical and, hence, a biosimilar is not a generic of a biological medicine. This is because the natural variability and more complex manufacturing of biological medicines do not make an exact replication of the molecular micro-heterogeneity possible. Biosimilars are generally cheaper than the original biologicals.

The new law is likely to lead to the automatic replacement of biologics with biosimilars by pharmacists, as is common practice with generics, where the G-BA has explicitly stated that the biologic and a specific biosimilar are interchangeable.

Both houses of Germany's parliament, the Bundestag and Bundesrat, voted in favour of the new law in June. The new framework is now likely to take effect some time in July.

There is to be a three-year period, until 2022, during which the substitution can only be made if explicitly permitted by the treating physician. In this three-year period, further scientific evidence on the interchangeability of biosimilars and experience with biosimilars in practice is to be collected. 

Arguments against the new law

The provisions on pharmacy-level substitution of biologics are aimed at encouraging greater use of biosimilars, but industry bodies including ProBiosimilars, as well as physicians at their 'parliament', theDeutscher Ärztetag, have criticised the measures.

Among the concerns raised are about which data the G-BA should assess the interchangeability of biosimilars on. There is a lack of data on the impacts of a substitution, including the results of treatment. This is why in most European countries the substitution of biologicals with biosimilars is not permitted without the consultation of the treating physician.

There are also concerns that pharmacy-level substitution would not allow patients or physicians to be adequately involved in the initial prescription of those medicines or when the biopharmaceutical therapy is changed.

Fears have also been expressed about a gap in the risk assessment regime that currently exists, under which all biosimilars are approved with a mandatory risk management plan. If the physician does not know which medicinal products the patient receives, due to a substitution in the pharmacy, it is not possible for doctors to fulfil their obligations with regard to the risk management plan and, in particular, to precisely assess the likely side effects.

In addition, industry has argued there are further risks that patients' medical records could be missing information where pharmacy-level substitution occurs and is not recorded on their file. This has potential implications for establishing liability and responsibility for damages in cases where things go wrong.

Industry has also argued that the new law is not necessary. They point out that biosimilars have, in recent years, already become more accepted and more common. The use of biosimilars has resulted in significant savings to the German health service and confidence and trust in biosimilars has already been won by doctors and patients as a result of major information campaigns by industry bodies and biosimilar manufacturers. Industry is concerned that this progress could be undermined by pharmacy-level substitution.

Warnings have also been issued about the impact pharmacy-level substitution will have on competition in the market. It is predicted that it will leave to a significant drop in the price of medicines. This may seem like a good thing for patients and the cost-effective operation of Germany's health system, but it threatens European manufacturers' ability to compete with companies based elsewhere in the world in the biosimilars market and could see companies move their manufacture of biosimilars to other jurisdictions. This could lead to a risk for the security of supply of medicines in Germany and present further risks to patient safety.

Industry's concerns are legitimate. As biosimilars are not identical to the respective reference medicinal product, other than in the case of generics, it should remain up to doctors to determine which medicinal products patients should receive after carefully assessing the complexity of the products available on the market.

Marc L. Holtorf and Dr Julia Traumann are Munich-based experts in life sciences at Pinsent Masons, the law firm behind Out-Law.